Forensic toxicology. analysis: identification of the substances, quantitative determination

Transcription

1 Forensic toxicology Toxon (Greek) bow Forensic toxicology is a part of forensic sciences concerned on the study of thousands of toxic substances or poisons and application this knowledge to the law purposes. Toxicology encompasses theoretical considerations, methods and procedures from many disciplines including analytical chemistry, biochemistry, epidemiology, pharmacodynamics, pathology, and physiology. Toxicology the study of the toxic or harmful effects of chemicals action of toxic substances occurrence of their harmful effects the symptoms and treatment of poisoned analysis: identification of the substances, quantitative determination "All substances are poisons: there are none to be not a poison. The right dose differentiates between a poison and a remedy" The toxic and the fatal dose Is not fixed for every drug or poison different people have a wide range of sensitivity or resistance and it may vary from time to time for one person LD 50 is determined in experiments on particular species of animals, so can t be simply extrapolated to humans It s almost impossible to calculate backward from a drug blood concentration what dose was used and when What substances are most frequently detected in autopsy samples in cases of suspected poisoning?

2 The list is not closed; it is continuously verified and modified medications sedatives, hypnotics benzodiazepines zolpidem, zopiclone barbiturates antidepressants TCA amitriptiline, imipramine, desipramine, clomipramine, doxepine SSRI fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram SNRI wenlafaxine IMAO moclobemide other mirtazapine, mianserine, trazodone neuroleptics phenotiazines (chlorpromazine, promazine, perazine, methotrimeprazine, perphenazine, thioridazine thioxanthenes (chlorprothixene, flu[enthixol, zuclopenthixol butyrophenones (haloperidol, droperidol) benzamides (sulpiride) atypical (clozapine, olanzapine, risperidone, quetiapine)

3 anticonvulsants (valproic acid, carbamazepine) cardiovascular β - antagonists - metoprolol, acebutolol, propranolol Ca - channel blockers - diltiazem, verapamil ACE enalapril, trandolapril, perindopril antiarrythmics propafenone glycosides digoxine, digitoxine diuretics indapamide, hydrohlorothiazide other trimetazidine drugs of abuse opioids opiates (morphine, codeine, heroine, oxycodone, buprenorphine) synthetic (tramadol, pethidine, pentazocine, methadone, phentanyls, propoxyphene) amfetamines amphetamine, metamphetamine designer drugs MDMA, MDA, MDEA, PMA, PMMA and many others cocaine

4 hallucinogenes LSD-25 psilocine, psilocybine mescaline salvinarine (Salvia divinorum) cannabinoids GHB (γ-hydroxybutyric acid analogue of GABA, acting like alcohol, popular date rape drug ) metamphetamine Marihuana, hashish cannabinols Δ9-THC (Δ9-tetrahydrocannabinol) main psychoactive substance in Cannabis sp.) GHB (γ-hydroxybutyric acid) white powder very soluble in water solution is colorless, water-like the taste is only light salty, undetectable in drinks, beer, food

5 alcohol-like acting, but doses are 100 x greater drug facilitating sexual assault no good screening tests is normally detected in the body legal highs ketones (analogs of amphetamines) mephedrone, methedrone, buphedrone, methylone, buthylone synthetic cannabinoids: (CP-47,497 i its 3 analogues ( Spice, K2 ) JWH-018, JWH-073, JWH-200, JWH-250, JWH-398 HU-210 acting like classic drugs (amphetamines, cannabinoids, deliriums) unknown toxicodynamics and toxicokinetics unpredictable symptoms especially when mixed with another drugs and alcohol lack of specific therapy pesticides phosphoroorganics (very toxic, inhibitors of acetylcholinoesterase) carbamates chlorinated hydroarbons

6 triazines phenylacetic acids derivatives pyretroides other ethylene glycol substitution of ethanol, fixed (non-volatile), of sweet-burning taste, available component of the cooler liquid, onset of intoxication similar to ethanol abuse toxic metabolites, causing excessive acidosis: glycol aldehyde, glyoxalic acid, glycolic acid (level of acidosis - prognosis as to life, not the blood concentration of glycol), lesion of kidneys deposition of calcium oxalate crystals (late metabolite) oliguria, anuria the quicker diagnosis the better prognosis for recovery (hemodialysis) Carbon monoxide chemical nature colorless and odorless gas slightly lighter than air easily penetrating source:

7 incomplete combustion (cookers, heaters, etc., insufficient ventilation, blocked chimney) car exhaust fumes (4-8% co) leakage from containers (ex. laboratory cylinders) fire (co toxicity is related to cyanide and hypoxia) Carbon monoxide mode of action displacement of oxygen from hemoglobin times higher affinity than oxygen very stable binding Carbon monoxide Toxicity Headache, nausea, drunken-like symptoms, coma Survivors: cystic degeneration of basal ganglia parkinsonism Death Cardio-respiratory failure (a kind of forensic asphyxia) Autopsy Cherry pink color of the lividity, intensive red color of the blood and tissues Carbon monoxide

8 Lab test Quick spectroscopy (very simple, but low sensitive method) Hospitals - CO-meters (not O2-meters!) Spectrophotometry (for ex. Wolff s method, Fretwurst-Meineck s metod) Gas chromatography (CO is converted and detected as methane) Carbon monoxide COHb (carboxyhaemoglobine concentration) Normal range (non-smokers) < 4% Smokers 10% Symptoms of toxicity ~20-30% (headaches, dizziness, nausea Loss of consciousness 40-50% death 50-60% Post-mortem signs suggesting poisoning Stomach remains of plants, mushrooms, tablets, capsules atypical color or/and smell (chemicals agents) gastritis and/or oesophagitis (irrigative agents) Liver

9 fatty changes, cirrhosis, necrosis (toxins of Amanita phalloidea, heavy metals, arsenic, Cl-derivatives of organic solvents, acetaminophen, NSAID) Kidneys Necrosis, inflammation (mercury, chromium, ethylene glycol) Lungs Oedema (corrosive gases) solutions of cyanide salts of sodium and potassium have a high ph value (11-12) and its very irritable for gastric mucosa Samples for toxicological analysis ml better collect small but fully filled bottle than half-empty large bottle urine vitreous body stomach with contents piece of liver bile kidney piece of brain piece of lung Lung and brain are important when volatile organic compounds are suspected

10 in some special cases Skin with underlying tissues intramuscular or subcutaneous injections Nails and hair suspicion of chronic poisonings - arsenic, thallium, antimony, mercury (hair must be orientated in one direction and root must be determined) living people control of abstinence from drugs anti-doping tests suspicion of exposure on GHB (rapes) material from exhumed bodies the same like from normal autopsy if body is not decomposed in case of decomposition tissues from abdomen cavity skeletal muscles embalming fluids may contains: formaldehyde, methanol, iodide compounds samples should be collected in glass clean tightly closed containers (jars, vials) all containers should be described name of deceased

11 date of autopsy name of the sample addition of any preservatives is forbidden samples should be refrigerated or (better) frozen is a passive process mean time of absorption after single bolus of alcohol: min. the gastric mucosa contains alcohol dehydrogenate which partly decomposes alcohol before it is absorbed into bloodstream The effects of alcohol Methods of alcohol analysis in biological samples (at least two): Widmark s method ADH enzymatic Gas chromatography preferred Widmark s method Simple, cheap Linear in the range of 0-5 promiles Unspecific (false positive due to other reducing agents: H2S, mercaptans, other alcoholes, aldehydes etc) Enzymatic ADH

12 EtOH +NAD EtCHO (acetaldehyde) +NADH Volume is not weight! Widmark s equation C blood alcohol concentration [ ] A amount of consumed alcohol [g]) p body weight [kg] r person body weight reduction coefficient volume of distribution individually calculated for each R resorption deficit (10-30%, ie R= 0,9 to 0,7) Rate of metabolism (β 60 ) 0,1 0,2 per hour may be lower or greater (up to 0,6 per hour in rare cases) may be different at the same person Alcohol-like acting substances (driving skills impairment) Road-side screening tests of saliva (immunochemical qualitative tests) Urine tests (immunochemical qualitative tests) Confirmatory examination blood/saliva/urine test conducted in laboratories: Forensic Medicine Departments (Medical Universities) Institute of Forensic Research (Cracow)

13 Central Laboratory of Police Substances to be monitored in blood according to the amendment to the Polish Law on Road Traffic opiates (LOD of morphine = 20ng/ml) amphetamine and derivates (LOD = 50ng/ml) cocaine and its metabolite benzoylecgonine (LOD of cocaine =50ng/ml) cannabinoids (LOD of Δ9THC = 2 ng/ml) benzodiazepines LOD = limit of detection